Inflammation and HIV Persistence

Investigator: Mike McCune, MD, PhD
Sponsor: American Foundation for AIDS Research (AmFAR)

Location(s): United States


Drs. McCune and Deeks will investigate the contribution of ongoing immune activation to the ability of HIV to persist. They hypothesize that a self-perpetuating, looping chain of events is established soon after HIV infection first occurs. The immune system is activated as it attempts to combat the infection, but this immune activation in turn fuels the ability of the virus to replicate and persist, resulting in a situation in which immune activation and viral replication feed one another. One enzyme that has been shown to be associated with AIDS progression is IDO, and Drs. McCune and Deeks believe it may play a critical role in maintaining the positive feedback between immune activation and viral growth. They will test whether disrupting this enzyme reduces the level of immune activation, which would in turn result in a decrease in viral persistence. They will also determine whether patients who naturally maintain extremely low levels of virus also have naturally low levels of IDO. If their hypothesis is correct, the results will point to a potential new therapeutic strategy that could both decrease levels of immune activation— itself associated with some of the disease conditions commonly seen in HIV infection— and lower the amount of virus that persists, bringing us closer to a functional cure.